1. Field of Invention
This invention relates to a method of inhibiting Type I allergic responses (Gell and Coombs classification of Immune Responses) in a living animal body with piperidinyl, pyrrolidinyl, and homopiperidinyl derivatives substituted on nitrogen by aryloxyalkyl radicals and otherwise substituted by aryl (or diaryl)-alkanol, aryl (or diaryl)-alkyl, aryl or (diaryl)cyano methyl and aryl (or diaryl)alkylidine radicals. The compounds prevent release of histamine and synthesis of 5-lypoxygenase metabolites as well as antagonize end organ effects of mediators involved in the immediate hypertensivity response and, as such, are useful in treating allergic phenomena which includes asthma, rhinitis, atopic dermatitis, chronic hives, allergic conjunctivitis, and the like.
2. Information Disclosure Statement
Various systemic anti-allergy agents have long been known prior to this invention including, among others, aminophylline, theophylline, corticosteroids, the disodium salt of 1,3-bis(2-carboxychromon-5-yloxy)-2-hydroxypropane, .alpha.-[(tertbutylamino)methyl]-3,5-dihydroxybenzylalcohol sulfate and oxatomide. The efficacy of some has suffered from undesirable side effects while others which are effective prophylactically are ineffective in acute manifestations of the allergic attack. By way of comparison, for example, the preferred compounds of the present invention are many times more potent than aminophylline and several times more potent than oxatomide.
Olefinic-4-substituted piperidino derivatives useful as antihistaminic, antiallergy agents and bronchodilators are represented by the formula: ##STR3## are disclosed in U.S. Pat. No. 3,862,173 wherein R represents hydrogen or forms a double bond, Y represents --CH.dbd.CH-- and Z represents thienyl, phenyl or phenyl substituted by halogen, alkyl, loweralkoxy, diloweralkylamino, pyrrolidino, piperidino, morpholino or N-loweralkylpiperazino. Compounds useful in the present invention differ in that an ether linkage is present and there is no unsaturation in the alkyl chain.
Diphenylmethylenepiperidineacetic acid derivatives useful as antiallergic, antihistaminic, and broncholytic agents are disclosed in European Pat. No. 48705B and have the formula: ##STR4## wherein Y is OH or NR.sub.1 R.sub.2 ; compounds useful in the present invention have an aryl group next to the ether oxygen.
U.S. Pat. No. 3,806,526 discloses 1-aroylalkyl-4-diphenylmethylpiperidines having antihistaminic, antiallergenic and bronchodilator activity. In contrast, the compounds useful in the present invention have an aryloxyalkyl radical on piperidine and pyrrolidine nitrogen rather than an aroylalkyl radical.
A number of the compounds useful in the present method of treating allergy have been disclosed specifically and under generic formulas in U.S. Pat. Nos. 3,922,276 and 3,956,296 as being useful as antiinflammatory agents, tranquilizers and sedatives. These activities are not suggestive of use in treating allergy.
The compound 4-diphenylmethylene-1-benzylpiperidine maleate is disclosed in Japanese Kokai No. 62,145,018 to be an antiallergy agent not liberating histamine. The compound is not encompassed by Formula I.